CONTEXT: Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. OBJECTIVE: This review critically examines the current evidence regarding risk-based PCa screening. EVIDENCE ACQUISITION: A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. EVIDENCE SYNTHESIS: Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. CONCLUSIONS: PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages.